170726-00-8Relevant articles and documents
Design, synthesis, and biological evaluation of 5-aminotetrahydroquinoline-based LSD1 inhibitors acting on Asp375
Yan, Jiangkun,Gu, Yanting,Sun, Yixiang,Zhang, Ziheng,Zhang, Xiangyu,Wang, Xinran,Wu, Tianxiao,Zhao, Dongmei,Cheng, Maosheng
, (2021/05/17)
The abnormal expression of lysine-specific histone demethylase 1 (LSD1) is associated with different cancer types, and LSD1?inhibitory activity seems to have high therapeutic potential in cancer treatment. Here, we report the design, synthesis, and biochemical evaluation of novel 5-aminotetrahydroquinoline-based LSD1 inhibitors. Among them, compounds A6, A8, B1–B5, and C4 showed preferable inhibitory effects on LSD1, with IC50 = 0.19–0.82 μM. Several potent compounds were selected to evaluate their antiproliferative activity on A549 cells and MCF-7 cells with a high expression of LSD1. The potential binding modes of the compounds were revealed through molecular docking to rationalize the potency of compounds toward LSD1. Our data recognized that the 5-aminotetrahydroquinoline scaffold may serve as a starting point for developing potent LSD1 inhibitors for cancer therapy.
Benzimidazole inhibitors of the protein kinase CHK2: Clarification of the binding mode by flexible side chain docking and protein-ligand crystallography
Matijssen, Cornelis,Silva-Santisteban, M. Cris,Westwood, Isaac M.,Siddique, Samerene,Choi, Vanessa,Sheldrake, Peter,Van Montfort, Rob L.M.,Blagg, Julian
supporting information, p. 6630 - 6639 (2013/01/15)
Two closely related binding modes have previously been proposed for the ATP-competitive benzimidazole class of checkpoint kinase 2 (CHK2) inhibitors; however, neither binding mode is entirely consistent with the reported SAR. Unconstrained rigid docking o
Discovery of potent isoxazoline glycoprotein IIb/IIIa receptor antagonists
Wityak, John,Sielecki, Thais M.,Pinto, Donald J.,Emmett, George,Sze, Jean Y.,Liu, Jie,Tobin, A. Ewa,Wang, Shuaige,Jiang, Biao,Ma, Philip,Mousa, Shaker A.,Wexler, Ruth R.,Olson, Richard E.
, p. 50 - 60 (2007/10/03)
Using the isoxazoline as a common structural feature, three series of glycoprotein IIb/IIIa receptor antagonists were evaluated, culminating in the discovery of XR299 (30). In an in vitro assay of platelet inhibition, XR299 had an IC50 of 0.24 μM and was a potent antiplatelet agent when dosed intravenously in a canine model. It was shown through X-ray studies of the cinchonidine salt 49 that the receptor required the 5(R)-stereochemistry for high potency. The ethyl ester prodrug of XR299, XR300 (29), was orally active in the dog.
